Brain Primer, Part 2: Pathophysiology of Neurodegeneration

Neurodegenerative diseases are characterized by progressive neuronal dysfunction, synaptic loss, and decline in cognitive, behavioral, or motor function. Understanding these disorders requires a foundational knowledge of neuroanatomy and physiology. Although normal aging leads to expected neuronal loss and changes in gray and white matter, neurodegenerative diseases are marked by systematic and progressive destruction of normal anatomy and function. Neurodegenerative diseases involve several key features, such as accumulation of amyloid-β plaques, tau hyperphosphorylation, microtubule destabilization, synaptic degeneration, and widespread neuroinflammatory responses driven by microglia and astrocytes. This article provides an integrated review of neurodegenerative mechanisms and provides a pathophysiologic overview of neurodegenerative diseases relevant to nuclear medicine and molecular imaging.